Functional analysis of CUL4/DDB1 ubiquitin E3 ligase in DNA damage response

2011 Fiscal Year Final Research Report

• Project/Area Number: 21510055
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Kanazawa University
• Principal Investigator: WAKASUGI Mitsuo 金沢大学, 薬学系, 助教 (80345595)
• Co-Investigator(Kenkyū-buntansha): MATSUNAGA Tsukasa 金沢大学, 薬学系, 教授 (60192340)
• Project Period (FY): 2009 – 2011
• Keywords: ゲノム / シグナル伝達 / DNA損傷応答 / ユビキチン

Research Abstract

The Cul4/DDB1 complex is a recently identified culling-RING ubiquitin ligase, which regulates DNA repair, DNA replication and transcription. We analyzed the potential functions of DDB1 in the responses to various DNA damaging agents using a conditional knockout DT40 cells. Furthermore, we found that the interaction between DDB1 and Cul4 is absolutely required for cell viability, suggesting an essential role of DDB1 as a component of Cul4/DDB1 ubiquitin E3 ligase.

Research Products

• [Journal Article] Establishment of a microplate for mattedcell-based immunoassay for rapid analysis of nucleotide excision repair ability in human primary cells (2012)
  • Author(s): Nishinaga M, Kurata R, Onishi K, Kuriyama K, Wakasugi M, Matsunaga T.
  • Journal Title: Photochem. Photobiol Volume: 88 Pages: 356-62
  • DOI: doi:10.1111/j.1751-1097.2012.01073.x
  • Peer Reviewed
• [Journal Article] The molecular basis of CRL4DDB2/CSA ubiquitin ligase architecture, targeting, and activation (2011)
  • Author(s): Fischer ES, Scrima A, Bohm K, Matsumoto S, Lingaraju GM, Faty M, Yasuda T, Cavadini S, Wakasugi M. Hanaoka F, Iwai S, Gut H, Sugasawa K, Thoma NH.
  • Journal Title: Cell Volume: 147 Pages: 1024-1039
  • DOI: doi:10.1016/j.cell.2011.10.035
  • Peer Reviewed
• [Journal Article] 休止期におけるヌクレオチド除去修復依存的な二次的DNA損傷の生成 (2011)
  • Author(s): 若杉光生, 松永司
  • Journal Title: 放射線生物研究 Volume: 46 Pages: 322-331
  • URL: http://www.naramed-u.ac.jp/~oncra/rbrc/
• [Journal Article] Role of interaction of XPF with RPA in nucleotide excision repair (2011)
  • Author(s): Fisher LA, Bessho M, Wakasugi M, Matsunaga T, Bessho T.
  • Journal Title: J Mol Biol Volume: 413 Pages: 337-346
  • DOI: doi:10.1016/j.jmb.2011.08.034
  • Peer Reviewed
• [Journal Article] SCFβ(TrCP) mediates stress-activated MAPK-induced Cdc25B degradation (2011)
  • Author(s): Uchida S, Watanabe N, Kudo Y, Yoshioka K, Matsunaga T, Ishizaka Y, Nakagama H, Poon RY, Yamashita K.
  • Journal Title: J Cell Sci Volume: 124 Pages: 2816-2825
  • DOI: doi:10.1242/jcs.083931
  • Peer Reviewed
• [Journal Article] Physical and functional interaction between DDB and XPA innucleotide excision repair (2009)
  • Author(s): Wakasugi M, Kasashima H, Fukase Y, Imura M, Imai R, Yamada S, Cleaver JE, Matsunaga T.
  • Journal Title: Nucleic Acids Res Volume: 37 Pages: 516-525
  • DOI: doi:10.1093/nar/gkn964
  • Peer Reviewed
• [Journal Article] Stress-activated mitogen-activated protein kinases c-Jun NH2-terminal kinase and p38 target Cdc25B for degradation (2009)
  • Author(s): Uchida S, Yoshioka K, Kizu R, Nakagama H, Matsunaga T, Ishizaka Y, Poon RY, Yamashita K.
  • Journal Title: Cancer Res Volume: 69 Pages: 6438-44
  • DOI: doi:10.1158/0008-5472.CAN09-0869
  • Peer Reviewed
• [Presentation] ヌクレオチド除去修復能の新規解析系の開発とその応用 (2012)
  • Author(s): 松永司
  • Organizer: 国立遺伝学研究所研究集会
  • Place of Presentation: 国立遺伝学研究所(静岡県)
  • Year and Date: 2012-02-10
• [Presentation] 休止期のヌクレオチド除去修復に伴う二重鎖切断の生成とATMシグナリング経路の活性化 (2011)
  • Author(s): 若杉光生
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2011-12-15
• [Presentation] 休止期細胞におけるヌクレオチド除去修復に依存した二重鎖切断の生成とATMシグナリング経路の活性化 (2011)
  • Author(s): 若杉光生
  • Organizer: 日本放射線影響学会第54回大会
  • Place of Presentation: 神戸商工会議所会館(兵庫県)
  • Year and Date: 2011-11-18
• [Presentation] ヒトG0期細胞におけるヌクレオチド除去修復に伴うATRとATMの活性化 (2010)
  • Author(s): 松永司
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会
  • Place of Presentation: 神戸国際展示場(兵庫県)
  • Year and Date: 2010-12-09
• [Presentation] ユビキチンE3リガーゼコンポーネントとしてのDDB1の機能解析 (2010)
  • Author(s): 若杉光生
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会
  • Place of Presentation: 神戸国際展示場(兵庫県)
  • Year and Date: 2010-12-08
• [Presentation] Essential role of DDB1 as a component of DDB1-CUL4 ubiquitin E3 ligase (2010)
  • Author(s): Kawaguchi, Y.
  • Organizer: 7th 3R(Replica-tion, Recombination and Repair) Symposium
  • Place of Presentation: Toyama international conference center(Toyama)
  • Year and Date: 2010-10-29
• [Presentation] 紫外線照射されたG0期細胞におけるヌクレオチド除去修復に依存した二次的DNA損傷の生成 (2010)
  • Author(s): 若杉光生
  • Organizer: 日本放射線影響学会第53回大会
  • Place of Presentation: 京都テルサ(京都府)
  • Year and Date: 2010-10-21
• [Presentation] DDB1-Cul4 E3リガーゼの機能解析 (2010)
  • Author(s): 松永司
  • Organizer: 国立遺伝学研究所研究集会
  • Place of Presentation: 国立遺伝学研究所(静岡県)
  • Year and Date: 2010-10-01
• [Presentation] 末梢血由来リンパ球を用いたヌクレオチド除去修復能診断系の開発 (2010)
  • Author(s): 松永司
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪府)
  • Year and Date: 2010-09-24
• [Presentation] DNA損傷によるChk1キナーゼの活性化とその制御 (2010)
  • Author(s): 松永司
  • Organizer: 平成22年度専門研究会
  • Place of Presentation: 京都大学原子炉実験所(大阪府)
  • Year and Date: 2010-09-11
• [Presentation] Modulation ofnucleotide excision repair in human cells (2010)
  • Author(s): Wakasugi, M.
  • Organizer: International Confernece on Radiation and Cancer Biology at Nagasaki 2010
  • Place of Presentation: Matsumoto Ryojun Auditorium Bawdwin Hall(Nagasaki)
  • Year and Date: 2010-02-18
• [Presentation] Histone H2AX phosphorylation triggered by nucleotide excision repair intermediates in quiescent cells (2009)
  • Author(s): Matsunaga, T.
  • Organizer: Keystone Symposia "Telomere Biology and DNA Repair"
  • Place of Presentation: RACV Royal Pines Resort(Australia)
  • Year and Date: 2009-10-11
• [Presentation] The role of caspase-Dependent Chk1 cleavage during apoptosis (2009)
  • Author(s): Matuura, K.
  • Organizer: Telomere Biology and DNA Repair
  • Place of Presentation: RACV Royal Pines Resort(Australia)
  • Year and Date: 2009-10-11
• [Presentation] 癌細胞におけるDNA損傷/複製ストレス後のChk1リン酸化の異常亢進 (2009)
  • Author(s): 松永司
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2009-10-01
• [Remarks]
  • URL: http://www.p.kanazawa-u.ac.jp/~iden/
• [Patent(Industrial Property Rights)] DNA損傷修復能力の簡便・迅速な検査方法 (2010)
  • Inventor(s): 松永司、西山千晶
  • Industrial Property Rights Holder: 金沢大学
  • Industrial Property Number: 特許、特願2010-155303
  • Filing Date: 2010-07-07